BACKGROUND Vasculature is formed by responding to homeostatic tissue demands including in developing hearts. Hypoxia generally stimulates vascular formation in which vascular endothelial growth factor A (VEGF-A) plays a critical role. Gestational hypoxia increases the risk of low intrauterine growth and low birth weight, both of which are known to increase the risk of the fetus developing cardiovascular defects. In fact, continuous gestational mild hypoxia (14% O2 ) from the mid-embryonic stage causes cardiac anomalies accompanied by a thinning compact layer in mice in vivo. Because coronary vasculature formation is necessary for compact layers to thicken, we hypothesized that defective coronary vessel organization is related to the thinning compact layer under gestational hypoxia conditions. RESULTS Continuous gestational mild hypoxia (14% O2 ) applied from embryonic day 10.5 (E10.5) reduced the expression of VEGF-A mRNA and proteins by over 60% in E12.5 hearts relative to control normoxic hearts. Formation of CD31-positive vascular plexus, blood islands, and microvessels in embryonic ventricles were stunted by gestational hypoxia compared to control E12.5 hearts. CONCLUSIONS Our results suggest that mild hypoxia (14% O2 ) does not induce coronary vessel organization or VEGF-A expression in developing mouse hearts, opposing the general effects of hypoxia-triggering vascular organization and VEGF-A expression.

中文翻译：

---

妊娠轻度缺氧小鼠胚胎心脏冠状动脉组织缺陷和 VEGF-A 减少。

背景技术脉管系统是通过响应包括在发育中的心脏在内的稳态组织需求而形成的。缺氧通常会刺激血管形成，其中血管内皮生长因子 A (VEGF-A) 起关键作用。妊娠期缺氧会增加宫内低生长和低出生体重的风险，这两者都会增加胎儿发生心血管缺陷的风险。事实上，从胚胎中期开始的持续妊娠期轻度缺氧（14% O2）会导致小鼠体内的心脏异常并伴有致密层变薄。因为冠状脉管系统的形成对于致密层增厚是必要的，我们假设有缺陷的冠状血管组织与妊娠缺氧条件下致密层变薄有关。结果从胚胎第 10.5 天 (E10.5) 开始持续的妊娠轻度缺氧 (14% O2) 使 E12.5 心脏中 VEGF-A mRNA 和蛋白质的表达相对于对照常氧心脏降低了 60% 以上。与对照 E12.5 心脏相比，胚胎心室中 CD31 阳性血管丛、血岛和微血管的形成因妊娠缺氧而受到阻碍。结论 我们的结果表明，轻度缺氧（14% O2）不会在发育中的小鼠心脏中诱导冠状血管组织或 VEGF-A 表达，这与缺氧触发血管组织和 VEGF-A 表达的一般影响相反。与对照 E12.5 心脏相比，胚胎心室中的微血管因妊娠缺氧而发育迟缓。结论 我们的结果表明，轻度缺氧（14% O2）不会在发育中的小鼠心脏中诱导冠状血管组织或 VEGF-A 表达，这与缺氧触发血管组织和 VEGF-A 表达的一般影响相反。与对照 E12.5 心脏相比，胚胎心室中的微血管因妊娠缺氧而发育迟缓。结论 我们的结果表明，轻度缺氧（14% O2）不会在发育中的小鼠心脏中诱导冠状血管组织或 VEGF-A 表达，这与缺氧触发血管组织和 VEGF-A 表达的一般影响相反。